Evidence map›Paper›PMID 17891135›Full record

ArticleNature biotechnology2007

Computational design of antibody-affinity improvement beyond in vivo maturation.

Shaun M Lippow, K Dane Wittrup, Bruce Tidor

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed
13.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 343 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. A modular platform for Sterically Masked Activated Cytokines (SMACks).Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Antibody Affinity Maturation by Computational Design.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  8. Review
  9. Article
  10. Multimodal diffusion for joint design of protein sequence and structure.Protein science : a publication of the Protein Society · 2025
    Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
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  20. Article

120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Shaun M LippowDepartment of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
K Dane Wittrup
Bruce Tidor
Massachusetts Institute of Technology · US

Funding

Engineered Antibody EGFR Antagonist Cancer TherapeuticsR01CA096504 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 2002 to 2017
$9.7M
Packing and Electrostatic Effects on Folding and BindingR01GM065418 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TIDOR, BRUCE · 2003 to 2012
$1.8M
Packing and Electrostatic Effects on Folding and BindingR56GM065418 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TIDOR, BRUCE · 2008 to 2008
$300k
NCI NIH HHS CA96504NCI NIH HHS R01 CA096504NIGMS NIH HHS GM65418NIGMS NIH HHS R01 GM065418NIGMS NIH HHS R56 GM065418
6 · The paper itself

Abstract

Antibodies are used extensively in diagnostics and as therapeutic agents. Achieving high-affinity binding is important for expanding detection limits, extending dissociation half-times, decreasing drug dosages and increasing drug efficacy. However, antibody-affinity maturation in vivo often fails to produce antibody drugs of the targeted potency, making further affinity maturation in vitro by directed evolution or computational design necessary. Here we present an iterative computational design procedure that focuses on electrostatic binding contributions and single mutants. By combining multiple designed mutations, a tenfold affinity improvement to 52 pM was engineered into the anti-epidermal growth factor receptor drug cetuximab (Erbitux), and a 140-fold improvement in affinity to 30 pM was obtained for the anti-lysozyme model antibody D44.1. The generality of the methods was further demonstrated through identification of known affinity-enhancing mutations in the therapeutic antibody bevacizumab (Avastin) and the model anti-fluorescein antibody 4-4-20. These results demonstrate computational capabilities for enhancing and accelerating the development of protein reagents and therapeutics.

Indexed as

Computer-Aided DesignAntibodiesAntibody AffinityAntigensGenetic EngineeringModels, BiologicalModels, MolecularMuramidaseMutationProtein BindingProtein ConformationYeastsAntibodiesAntigensMuramidase

Identifiers

PMID17891135
PMCPMC2803018
OpenAlexW2083028331

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.